Breastfeeding improves health outcomes in infancy, including risks for eczema and gastrointestinal infections, but the long-term physiological effects of breastfeeding on child health are less clear. Among the most controversial purported benefits of breastfeeding are long-term effects on neurocognitive function and asthma. Existing evidence is largely based on observational studies, which are prone to measurement error, publication bias and reverse causality. In addition, substantial differences between mothers who do and do not choose to breastfeed may confound results from observational studies, so it is difficult to determine whether the observational associations of breastfeeding duration with child health outcomes are causal or have alternative explanations. The unbiased effects of breastfeeding can probably only be convincingly demonstrated in a randomized controlled trial (RCT). While it is not feasible to randomize healthy term infants to be breast or bottle fed, it is possible to randomize mother-child pairs to a breastfeeding promotion intervention. The Promotion of Breastfeeding Intervention Trial (PROBIT, ISRCTN37687716), the largest randomized trial of breastfeeding ever conducted, successfully increased breastfeeding duration and exclusivity among over 17,000 mother- infant pairs. The PROBIT intervention resulted in high rates of prolonged and exclusive breastfeeding;for example at 3 months, 43% of intervention mothers were exclusively breastfeeding compared with 6% of mothers in the control arm. The most plausible mechanism for any observed differences between the intervention groups is that the increased breastfeeding, caused by the breastfeeding promotion intervention, is the cause of differences between the intervention groups. Previous phases of PROBIT have demonstrated high rates of follow-up and valid, research-standard measurement of outcomes. The PROBIT trial thus offers a unique opportunity to obtain un-confounded estimates of the influence of breastfeeding on child health outcomes. Our current proposal is based on the 15-year follow-up of children enrolled in PROBIT. In an intention-to-treat analysis that compares the randomized arms, we will estimate the unconfounded, causal effects of prolonged, exclusive breastfeeding on child neurocognitive development (verbal and non-verbal cognition, visual acuity) and lung function. Our hypotheses build and improve on important findings from a previous follow-up of PROBIT children. Understanding the causal effects of breastfeeding is important to maximize the population- wide impact of guidelines focusing on early nutrition, by providing robust data, ensuring consistent conclusions, and minimizing potential harms. PUBLIC HEALTH RELEVANCE: Exclusive breastfeeding is recommended for 6 months, but only 60% of women in the US initiate breastfeeding and just 20% breastfeed to any extent for 6 months. Robust evidence supporting the long-term benefits of breastfeeding for child cognition, vision, and lung function may increase acceptance and uptake of national and local policies to promote breastfeeding.